1. Field of Invention
The inventive subject matter relates to a codon optimized nucleic acid sequence of Bacillus anthracis protective antigen (PA). The method of codon optimization of the gene is aimed at improving expression in mammals, including humans, as well as enhancing immunogenicity against endogenously produced PA protein. The inventive construct, incorporated into DNA expression systems, can be useful as a component of immunogenic compositions against B. anthracis, such as vaccines.
2. Background Art
B. anthracis, the etiological agent of anthrax, is a spore-forming, gram positive bacterium. Infection can occur through a variety of routes including cutaneous and gastrointestinal, however, inhalational anthrax is the most widely recognized and feared (Baillie, J. Appl Microbiol., 91: 609-613 (2001)). Following inhalation, the majority of the aerosolized spores are immediately phagocytized by alveolar macrophages and transported through the lymphatic channels to hilar and tracheobronchial lymph nodes. This rapidly leads to the multiplication and systemic circulation of vegetative bacilli. It is believed that en route to these regional lymph nodes the spores begin to germinate and multiply within the macrophage.
Advanced stages of infection are predicated on B. anthracis' anti-phagocytic capsule and the secretion of a tripartite exotoxin consisting of a cell binding component, Protective Antigen (PA), which binds to two enzymatically active subunits: Lethal Factor (LF) or Edema Factor (EF) to form lethal toxin (LeTx) and edema toxin (EdTx), respectively. The currently available licensed human vaccine for B. anthracis (BioThrax) is a filtered extract from B. anthracis absorbed to alum and is primarily composed of PA.